Supplementary Figure 5: Enhancer invasion shapes transcriptional sensitivity to MYCN perturbation in neuroblastoma. | Nature Genetics

Supplementary Figure 5: Enhancer invasion shapes transcriptional sensitivity to MYCN perturbation in neuroblastoma.

From: Enhancer invasion shapes MYCN-dependent transcriptional amplification in neuroblastoma

Supplementary Figure 5

a, Top, plot showing the top 5,000 genes in SHEP-21N ranked by total proximal MYCN signal. Bottom, dot plot of the percentage of enhancer contribution, the size of contributing MYCN binding, the density of contributing MYCN, and the area under the curve of contributing MYCN binding with a best fit line superimposed (loess correlation). b, Top, plot showing the top 5,000 genes across four neuroblastoma cell lines ranked by total proximal MYCN signal. Bottom, dot plot of the percentage of enhancer contribution, the size of contributing MYCN binding, the density of contributing MYCN, and the area under the curve of contributing MYCN binding with a best fit line superimposed (loess correlation). c, Standard (left) and cell count (right) normalized levels of the RPL22, HAND2, and ID2 transcripts during MYCN shutdown. Units are FPKM and cell-count-normalized FPKM, respectively, for triplicate biological replicates. Error bars represent s.d. d, Standard normalized log2 fold change (versus 0 h) of gene expression changes during MYCN shutdown in the SHEP-21N system. Genes are grouped according to rank-ordered MYCN proximal load (promoters and enhancers). Error bars represent the 95% confidence interval (CI) of the mean. e, Box plots of the log2 fold change (versus 0 h) of the amount of RNA Pol II (ChIP-Rx, before scaling) at the TSS (left) and gene body (right) of genes grouped according to rank-ordered MYCN proximal load. Significance is denoted by Welch’s two-tailed t test: ***P < 1 × 10–9, **P < 1 × 10–6, *P < 1 × 10–3. f, Box plots of the log2 fold change (versus 0 h) of the amount of RNA Pol II (ChIP–seq) at the TSS (left) and gene body (right) of genes grouped according to rank-ordered MYCN proximal load. Significance is denoted by Welch’s two-tailed t test: ***P < 1 × 10–9, **P < 1 × 10–6, *P < 1 × 10–3.

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